Title:Transcriptomic Insights into the Oxidative Response of Stress-Exposed Aspergillus fumigatus
Volume: 19
Issue: 20
Author(s): Emilie Frealle, Cecile-Marie Aliouat-Denis, Laurence Delhaes, David Hot and Eduardo Dei-Cas
Affiliation:
Keywords:
Apergillus fumigatus, microarrays, next-generation sequencing, transcriptomics, antioxidant enzymes, secondary metabolites.
Abstract: NADPH-oxidase mediated production of Reactive Oxygen Species (ROS) by alveolar macrophages and neutrophils is a critical
mechanism for immune defence against Aspergillus fumigatus. Fungal oxidative stress response includes enzymatic response by superoxide
dismutases (SOD), catalases, and enzymes from the thioredoxin and glutathione systems, which are regulated by the transcription
factor Yap1. Secondary metabolites are also involved in defense against ROS. Some of the secondary metabolite clusters are controlled
by the transcriptional regulator LaeA.
The redundancy of antioxidant systems, and the variable impact of SOD or catalase gene deletions on in vitro oxidative stress sensitivity
and in vivo virulence suggest a complex regulation of oxidative stress response in A. fumigatus, making high-throughput approaches,
such as microarray or next generation sequencing (NGS), highly relevant to study their respective role. These approaches have been
widely applied to A fumigatus, in order to characterize its metabolic response to different stresses mimicking in vivo conditions (such as
antifungals, or neutrophils), or to transcription factor deletion (including LaeA). In some studies, oxidative stress response process and
antioxidant enzymes have been identified as key metabolic pathways. However, oxidative stress response has not been analyzed systematically
and a further data analysis could be helpful to clarify the role of A. fumigatus antioxidant systems and, potentially, to identify new
drug targets.
In this review, we synthesized available A. fumigatus microarrays and NGS data, focusing on the role of antioxidant systems. We analyzed
the different methodologies that were used for transcriptomic analysis, and we compared biological processes and antioxidant system
modulations in A. fumigatus exposed to stress.
